Professor Alastair O'Brien's research is dedicated to improving management of infection in liver cirrhosis, which is the most common cause of death in these patients. His laboratory work identified the first molecular mechanism (elevated Prostaglandin E2 (PGE2)) underlying immune suppression in cirrhosis and they completed a national clinical trial to investigate whether albumin infusions could antagonize PGE2. The ATTIRE Feasibility and Randomised Clinical Trials (Albumin to prevent infection in chronic liver failure) showed that targeted albumin infusions had no benefit for hospitalised patients with decompensated cirrhosis. Albumin was first used in cirrhosis 70 years ago and is used for fluid resuscitation globally, however, it is 40 times the cost of other fluids. ATTIRE has led to restricted use and firm adherence to evidence-based guidelines, rather than the unrestrained prescribing previously and has changed the focus of albumin research, with infusions now investigated in outpatients not hospitals.

From 2019, Alastair led the ASEPTIC trial (Primary Antibiotic prophylaxis using co-trimoxazole to prevent SpontanEous bacterial PeritoniTIs in Cirrhosis, NIHR) which completed recruitment in 2023 (442 patients from 45 hospitals), with results available in April 2025. This is the largest trial of antibiotic prophylaxis in cirrhosis and manged to successfully recruit during the COVID pandemic, which is considered a massive achievement internationally. Furthermore, NICE have asked Professor O'Brien's laboratory to notify them when the study is published so that they can update their cirrhosis guidelines according to the results.

ATTIRE was identified as a success by the NIHR Clinical Research Network in recruiting from hospitals with high disease prevalence but new to clinical research. Patients with cirrhosis are under-represented in clinical trials, especially those with alcohol induced liver disease, as they are believed to be unreliable and those hospitalised with complications of cirrhosis are frequently considered too unwell to participate. Our studies have proven both assumptions wholly incorrect and their successful delivery (along with STOPAH) catalysed a large increase in research activity such that the UK has become a world leader in trials for patients with cirrhosis.